The hypothesis that the pancreatic beta cell is a primary site of pathology in human and experimental diabetes, and the knowledge that the beta cell population is affected by genetic background and by diet and responds to toxic and infectious agents, has directed our attention to the need for further study of an experimental model of juvenile type diabetes. Multiple small injections of streptozotocin in mice produce pancreatic insulitis, with progression to nearly complete beta cell destruction and diabetes mellitus. Three parameters of this model appear to be involved: hyperglycemia; an inflammatory islet lesion suggesting a cell-mediated immune reaction; and a proliferation of C-type virus within the beta cells. This request is for support of several research projects designed to expand our studies and to define more precisely the syndrome of multiple low dose streptozotocin as they specifically relate to the three major components (hyper-glycemia, insulitis, and C-type virus).